The goal of this proposal is to determine the role that neural activity plays in the development of circuits within the retina. Specifically, we hope to gain insight into how signaling through NMDA receptors (NMDARs) contributes to the formation of excitatory circuits. We hypothesize that signaling through NMDARs is required for synapse formation between cone bipolar cells (cBCs) and retinal ganglion cells (RGCs). To test this hypothesis we have developed two aims. In Aim 1, we will use transgenic mouse lines in which a single functional type of RGC is labeled to determine whether the subunit composition of NMDARs (eg. NR2A, NR2B) changes during development in each of several RGC types. In Aim 2, we will use a mouse line in which RGCs lack functional NMDARs to determine whether NMDARs contribute to synapse formation between cBCs and RGCs. In the course of this work, we hope to improve our understanding of how synapse formation is regulated in the retina. Our findings will provide crucial insight that will guide future research aimed at developing strategies to promote synapse formation. These strategies might prove invaluable in developing therapies to treat the many retinal diseases that stem from cell death. PUBLIC HEALTH RELEVANCE: In this study, we propose to test whether specific electrical and chemical activity is necessary for normal development of the connections between cells in the mammalian retina. This will extend our understanding of how the retina gives rise to sight and, ultimately, might lead to improvements in the treatment of both genetic and age-related retinal disorders that cause blindness.